This invention relates to compositions having gas-transporting properties, and more particularly to aqueous dispersions of perfluoronated polycyclic hydrocarbons as the major gas-transporting agent and surfactants for dispersing the perfluorinated polycyclic hydrocarbon in the aqueous medium. The compositions maintain a range of very small particle size over long periods of time, of the order of 6 months to a year or more, and therefore provide the good stability required for use of the compositions as blood substitutes, organ perfusates and other uses wherein low particle size and stability for extensive periods is important.
A continuing problem in the search for compositions useful as blood substitutes or other applications based on gas-carrying properties, including transfer of oxygen, carbon dioxide and other gases, is stability of the composition. The leading candidate to date for synthetic blood applications is an aqueous emulsion of F-decalin and F-tripropylamine, as the gas-transporting ingredients, and as emulsifiers a combination of a polyoxyethylene-polyoxypropylene copolymer [commercially available as "Pluronic (trademark) F-68"] and a yolk phospholipid. While this composition is satisfactory with respect to gas-transfer capabilities, the components of the composition agglomerate and eventually separate unless the composition is frozen immediately after preparation and maintained in a frozen state until use. This requirement vastly limits applications and value of the composition since in many applications and environments the composition cannot be adequately maintained in a frozen state. Typical circumstances include emergency field use by the military.
Since small particle size of the gas transfer ingredients of the compositions is important in synthetic blood uses, stability must necessarily be defined in terms of maintenance of a low particle size range over the useful life of the composition, including storage time. While small particle size has been shown to be maintainable for extensive periods in the aforesaid compositions based on F-decalin, the utility of such compositions is drastically limited by the requirement that the compositions be maintained in a frozen state until use.
Typical of the literature describing synthetic blood compositions are the following U.S. Pat. Nos. 3,911,138 to L. C. Clark, Jr.; 4,105,798 to R. E. Moore and L. C. Clark, Jr.; 3,823,091 to Samejima et al; 3,962,439 to Yokoyama et al; 3,993,581 to Yokoyama et al; 3,828,085 to Price et al; and 3,778,381 to Rosano et al. None of the foregoing patents discloses or suggests gas transporting compositions for blood substitute, organ perfusate and therapeutic applications, wherein all of the requirements of an optimum blood substitute are exhibited, including high gas transfer capability, low retention time in the mammalian body, non-toxicity, low particle size range and, particularly, capability of being stored for extensive periods of time at room temperature without undue particle agglomeration or separation.